PROVIDED. Scientific: Urinary incontinence (Ul) is a common problem in middle-aged and older women that resultsin tens of billions of dollars in health care expenditures and has been associated with an increased risk of nursing home admissions, falls, and decreased quality of life. The proposed epidemiologic study would follow a well-characterized cohort of 2000 women original enrolled under the Reproductive Risks of Incontinence Study at Kaiser (RRISK). The RRISK cohort is probably unique in being apopulation-based prospective cohort with excellent representation of Black, Asian, Hispanic and non-Hispanic Whitewomen devoted to the study of voiding dysfunction and incontinence. It is also part of the UCSF SpecializedCenter of Research which includes a laboratory-based research group investigating underlying mechanisms for voiding dysfunction and incontinence. The proposed study will continue this highly successful collaboration by investigating questions that have arisen from our clinical and basic science investigations underthe current SCOR. The overall goal of our proposed study is to advance our understanding of the mechanisms of voiding dysfunction and Ul and to facilitate the translational development of novel approaches totreatment and prevention. Specifically, we propose to address the following 6 questions: what is the basis for the two to three fold higher prevalence of stress incontinence in White, comparedto Black or Asian women; what is the longitudinal relationship between pre-diabetes and Ul; do adipocytokines explain the relationship between obesity and incontinence; do phytoestrogens increase the risk of Ul; are estrogen receptor gene polymorphisms risk factors for Ul; and what are risk factors for incident Ul and progression of existingUl. Lay Language: Urinary incontinence is a common problem for which there are limited treatments. Ourstudy will investigate several promising areas to increase our understanding of the mechanisms underlying incontinence and suggest new approaches to treatment and prevention. We will study an ethnicallyand racially diverse group of 2000 women to determine the nature of the recently reported relationship between pre-diabetes and incontinence, and to investigate 3 possible new risk factors for incontinence: adipocytokines (substances secreted by fat cells), phytoestrogens (plant molecules with estrogen-like effects) and genetic variations in estrogen receptors (molecules that allow estrogen to act on cells).